The present invention relates to quinolinecarboxylic acid derivatives or salts thereof having excellent antibacterial action and photostability, and antibacterial agents containing the same.
Since compounds having quinolinecarboxylic acid as a basic skeleton are excellent in antimicrobial activity and broad antibacterial spectrum, a number of useful ones as synthetic antibacterial agents are known. Among them, norfloxacin (Japanese Patent Application Laid-Open No. Sho 53-141286), enoxacin (Japanese Patent Application Laid-Open No. Sho 55-31042), ofloxacin (Japanese Patent Application Laid-Open No. Sho 57-46986), ciprofloxacin (Japanese Patent Application Laid-Open No. Sho 58-74667), tosufloxacin (Japanese Patent Application Laid-Open No. Sho 60-228479) and the like have wide clinical utility as therapeutic agents for infectious diseases.
These compounds are, however, still insufficient in antimicrobial activity, intestinal absorption and metabolic stability, and in addition, they are known to cause cytotoxicity or photodermatosis. Thus, many problems remain unsolved.
It is reported that some quinolinecarboxylic acid compounds are not stable to light and happen to be colored or decomposed when exposed to light. Consideration must be taken for some of their dosage forms so as to pharmaceutically overcome this drawback.
An object of the present invention is therefore to provide a compound which has reduced side effects, is excellent in antimicrobial activity, intestinal absorption and metabolic stability and is optically stable.
Under such circumstances, the present inventors found that pyridonecarboxylic acid derivatives each represented by the following formula (I): 
[wherein R1 represents a hydrogen atom or a carboxyl protective group; R2 represents a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; R3 represents a hydrogen atom or a halogen atom; R4 represents a hydrogen atom or a halogen atom; R5 represents a halogen atom or an optionally substituted saturated cyclic amino group; R6 represents a hydrogen atom, a halogen atom, a nitro group, or an optionally protected amino group; X, Y and Z may be the same or different and respectively represent a nitrogen atom, xe2x80x94CHxe2x95x90 or xe2x80x94CR7xe2x95x90 (wherein R7 represents a lower alkyl group, a halogen atom, or a cyano group) (with the proviso that at least one of X, Y and Z represents the nitrogen atom), and W represents a nitrogen atom or xe2x80x94CR8xe2x95x90 (wherein R8 represents a hydrogen atom, a halogen atom, or a lower alkyl group)], or salts thereof have excellent antibacterial properties against both gram negative and gram positive bacteria and have a markedly low toxicity so that they are useful as a synthetic antibacterial agent, and already filed an international application (WO97/11068) for it.
The present inventors have proceeded with a further investigation on photostability. As a result, it has been found that among the above-described pyridonecarboxylic acid derivatives (I), 1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-hydroxyazetidin-1-yl)-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (Compound 1) of the following formula: 
which has a 6-amino-3,5-difluoropyridinyl group on position 1, a hydroxyazetidinyl group on position 7 and a methyl group on position 8, or salt thereof has markedly high photostability so as to permit formulation into any dosage form as a preventive or remedy of various infectious diseases, while sustaining strong antimicrobial activity and low toxicity inherent to the pyridonecarboxylic acid derivatives of the formula (I), leading to the completion of the invention.
In the present invention, there is thus provided 1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-hydroxyazetidin-1-yl)-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid or salt thereof.
In the present invention, there is also provided a drug comprising said compound or salt thereof as an active ingredient.
In the present invention, there is also provided a pharmaceutical composition comprising said compound or salt thereof and a pharmaceutically acceptable carrier.
In the present invention, there is also provided the use of said compound or salt thereof for the preparation of a drug.
Furthermore, in the present invention, there is also provided a method for treating infectious diseases, characterized by administering said compound or salt thereof.